Despite a great deal of cognitive psychology and cognitive neuroscience research, there are still major gaps in our knowledge of how information is stored and used in working memory (WM). In particular, it is not clear whether certain types of WM tasks, such as those involving either integration or cross-domain storage of maintained content, rely upon distinct cognitive operations that are subserved by specialized brain regions. For example, recent work has suggested that a particular brain region, the anterior prefrontal cortex (aPFC), may serve as the neural substrate of the episodic buffer (Prabhakaran et al, 2000) - a domain-general storage site for maintaining integrated multi-domain content (Baddeley, 2000). Yet other work has suggested that this brain region might be involved in related WM functions, such as preparation for integration, interference prevention during integration conditions and retrieval of WM information out of the focus of attention, rather than WM storage per se. The goal of this project will be to test these competing hypotheses of aPFC function in WM more directly and systematically. Specifically, we aim to: - Test whether aPFC is selectively activated by maintenance of integrated versus unintegrated multi- domain information. We will replicate and extend the previous work of Prabhakaran et al. using an improved experimental design and event-related fMRI methods that enable decomposition of activation during different stages of WM trials. - Test whether aPFC activation during a cross-domain WM task involves other functions beyond storage. We will use a novel presentation method that enables close matching of integration and non- integration conditions and the ability to examine brain activity in preparation for, as well as during and after integration of information in WM. - Test whether aPFC activation specifically reflects attentional filtering operations that either facilitate or over-ride tendencies for cross-domain integration and maintenance. We will vary memory load and attentional instructions, delivered with pre- and post-stimulus cues, to isolate effects of attention during encoding and maintenance to observe whether filtering irrelevant or integrating relevant WM content requires aPFC activity. This research will increase knowledge of WM function and the brain structures that subserve it. WM ability is crucial for cognitive operations such as speech and reasoning. Knowledge about WM processes lead to better treatment for attention disorders and improved educational techniques. [unreadable] [unreadable] [unreadable]